臺灣首例利用硼中子捕獲方式治療復發性顱內惡性膠質細胞瘤之經驗

Salvage Boron Neutron Capture Therapy (BNCT) for the First Case of Recurrent Glioblastoma in Taiwan

背景：報告台灣首例利用硼中子捕獲方式來治療復發性之顱內惡性膠質細胞瘤。
方法：患者是一位 51 歲男性，於 2016 年一月首次開顱手術後診斷為位在右側大腦頂葉之惡性膠母細胞瘤（Glioblastoma; WHO grade IV），術中亦植入化學藥物晶片（Gliadel Wafer），後續也完成標準性之合併放化學治療（60 格雷 /30 次 X 光放射以及每日口服Temozolomide 六週）以及加強性口服 Temozolomide六個月，然腦部腫瘤仍很快於 2017 年一月復發，復發後雖施予標靶治療 Avastin（Bevacizumab）然腫瘤仍快速增長，因此團隊透過本院人體試驗委員會審查以及衛福部食品藥物管理署核准，針對此個案執行補救性硼中子捕獲治療（Boron Neutron Capture Therapy; BNCT）之緊急醫療處置。在執行該項治療前 , 患者已完成分析用之特殊正子攝影檢查（FBPA-PET），該項檢查呈現出腫瘤與血液中含硼藥物的積聚比例為 3.37（Tumor/Blood ratio;T/B ratio），符合治療的基本需求。患者遂於 2017 年 3 月 24 日在清華大學水池式反應器（Tsing-Hua Open Pool Reactor; THOR）接受完整硼中子捕獲之腫瘤治療處置。患者於執行治療的整體過程中總共接受了 400 毫克 / 體重公斤重的連續性藥物 L-BPA（p-borono-L-phenylalanine）靜脈滴注處置。執行超熱中子照射前之血液中硼濃度為 26.18 ppm。患者整體腫瘤所接受之平均劑量為19.18 單位之生物等效劑量（Gray-Equivalent; Gy-E）。
結果：本次個案在接受過硼中子捕獲治療的處置後，初期一個月腫瘤體積雖無明顯變化，然而後續之磁振造影頻譜（Magnetic Resonance Spectroscopy; MRS）分析中顯示腫瘤組織呈現壞死狀態，但周邊正常組織鮮少傷害性。
結論：硼中子捕獲治療對於復發性之顱內惡性膠質細胞瘤是一可以突破發展之補救性治療方式。

Background: To report the treatment experience and results of the first BNCT patient with recurrent glioblastoma in Taiwan.
Methods: The 51-year-old male patient is a case diagnosed as right parietal glioblastoma after craniotomy in January, 2016. During surgery, he also received Carmustine wafer (Gliadel®) insertion. After surgery, he underwent concurrent chemoradiotherapy (CCRT) with focal 60 Gy/30 fractions and daily oral Temozolomide. After CCRT, he also received adjuvant Temozolomide for six months. However, tumor relapse was noted one year later in January, 2017. Although target therapy, Bevacizumab (Avastin®), was prescribed, the tumor still progressed rapidly. Therefore, salvage BNCT was applied and approved by IRB (Institutional Review Board) of Taipei Veterans General Hospital and Taiwan’s Food and Drug Administration (TFDA). BNCT was performed at the Tsing-Hua Open Pool Reactor (THOR) on March 24th, 2017. Before BNCT, his FBPA-PET revealed a 3.37 Tumor/Blood ratio. He continuously received a total dose of 400 mg/ kg of body weight of L-BPA(p-borono-L-phenylalanine) via intravenous dripping during the treatment. Before epithermal neutron irradiation, the blood boron concentration was 26.18 ppm. Mean tumor dose of GTV was prescribed as 19.18 Gy-E by the THOR plan.
Results: One month after BNCT, MRS (magnetic resonance spectroscopy) revealed that the previous tumor bulk became massive necrotic tissue with limited surrounding normal tissue toxicities.
Conclusion: BNCT is an effective salvage management for recurrent intracranial malignant glioma.